PMID- 17891687 OWN - NLM STAT- MEDLINE DCOM- 20090303 LR - 20181201 IS - 2148-5607 (Electronic) IS - 1300-4948 (Linking) VI - 18 IP - 3 DP - 2007 Sep TI - Central effects of glucagon-like peptide-1 on cold-restraint stress-induced gastric mucosal lesions. PG - 150-6 AB - BACKGROUND/AIMS: Intracerebroventricular (i.c.v.) glucagon-like peptide-1 (GLP-1) has been shown to prevent gastric mucosal lesions induced by reserpine and ethanol. Here, we aimed to investigate the effects of i.c.v. GLP-1 on stress-induced gastric mucosal lesions and the mechanisms which may mediate these effects. METHODS: Rats were equipped with intravenous and i.c.v. cannulas under ether anesthesia. To induce cold-restraint stress, rats were kept individually in wire cages, specifically prepared according to their sizes, at 7-9 degrees C for 5 hours. They were then decapitated, and their stomachs were removed and scored for mucosal damage. GLP-1 (1, 10, 100, 1000 ng/10 microl; i.c.v.) was injected 5 min before cold-restraint stress induction. Rats were pretreated with exendin-(9-39) (2.5 ng/10 microl; i.c.v. and 250 ng/kg; intraperitoneal [i.p.]), calcitonin gene-related peptide (CGRP)-(8-37) (10 microg/kg; i.p.), N(G)-nitro-L-arginine methyl ester (L-NAME) (3 mg/kg; i.v.), indomethacin (5 mg/kg; i.p.) and atropine (1 mg/kg; i.p.) to investigate mechanisms which may mediate the gastroprotective effect of GLP-1. RESULTS: GLP-1 (1000 ng/10 microl; i.c.v.) significantly prevented gastric mucosal lesions induced by cold-restraint stress (p<0.01). Intracerebroventricular (i.c.v.), but not i.p., injection of exendin-(9-39) significantly blocked the gastroprotective effect of the peptide (p<0.05). Pretreatment with CGRP-(8-37), L-NAME and indomethacin also prevented the gastroprotective effect of i.c.v. GLP-1 (p<0.05, p<0.05 and p<0.01, respectively), while pretreatment with atropine did not prevent the gastroprotective effect of the peptide. CONCLUSIONS: We conclude that i.c.v GLP-1 inhibits the gastric mucosal damage induced by cold-restraint stress via the activation of its specific receptors, and CGRP, nitric oxide and prostaglandins, but not cholinergic muscarinic receptors, mediate this effect. FAU - Isbil Buyukcoskun, Naciye AU - Isbil Buyukcoskun N AD - Department of Physiology, Uludag University, School of Medicine, Bursa. nisbil@uludag.edu.tr FAU - Gulec, Guldal AU - Gulec G FAU - Cam Etoz, Betul AU - Cam Etoz B FAU - Ozluk, Kasim AU - Ozluk K LA - eng PT - Journal Article PL - Turkey TA - Turk J Gastroenterol JT - The Turkish journal of gastroenterology : the official journal of Turkish Society of Gastroenterology JID - 9515841 RN - 0 (Anti-Inflammatory Agents, Non-Steroidal) RN - 0 (Enzyme Inhibitors) RN - 0 (Incretins) RN - 0 (Parasympatholytics) RN - 0 (Peptide Fragments) RN - 119911-68-1 (calcitonin gene-related peptide (8-37)) RN - 5313W10MYT (exendin (9-39)) RN - 7C0697DR9I (Atropine) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - JHB2QIZ69Z (Calcitonin Gene-Related Peptide) RN - V55S2QJN2X (NG-Nitroarginine Methyl Ester) RN - XXE1CET956 (Indomethacin) SB - IM MH - Animals MH - Anti-Inflammatory Agents, Non-Steroidal/pharmacology MH - Atropine/pharmacology MH - Calcitonin Gene-Related Peptide/pharmacology MH - *Cold Temperature MH - Enzyme Inhibitors/pharmacology MH - Gastric Mucosa/*drug effects/physiopathology MH - Glucagon-Like Peptide 1/*pharmacology MH - Incretins/*pharmacology MH - Indomethacin/pharmacology MH - Injections MH - Male MH - NG-Nitroarginine Methyl Ester/pharmacology MH - Parasympatholytics/pharmacology MH - Peptide Fragments/pharmacology MH - Rats MH - Rats, Wistar MH - Restraint, Physical MH - Stress, Physiological/*physiology EDAT- 2007/09/25 09:00 MHDA- 2009/03/04 09:00 CRDT- 2007/09/25 09:00 PHST- 2007/09/25 09:00 [pubmed] PHST- 2009/03/04 09:00 [medline] PHST- 2007/09/25 09:00 [entrez] PST - ppublish SO - Turk J Gastroenterol. 2007 Sep;18(3):150-6.